crossing96/oncoscreening huggingface dataset:
Prognostic and Predictive Value of Fibroblast Growth Factor Receptor Alterations in High-grade Non-muscle-invasive Bladder Cancer Treated with and Without Bacillus Calmette-Guérin Immunotherapy.	BACKGROUND: Limited data are available on the prognostic and predictive value of fibroblast growth factor receptor alterations (FGFRa) relative to clinical outcomes in patients with non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To determine whether FGFRa may be clinically useful in stratifying for treatment response in a real-world cohort of patients with pT1 NMIBC treated and untreated with bacillus Calmette-Guérin (BCG) instillation therapy. DESIGN, SETTING, AND PARTICIPANTS: A pooled dataset of matched clinical and genomic data (1992-2015) for pT1 NMIBC patients was assessed by the Bladder Cancer Research Initiative for Drug Targets in Germany consortium. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Key efficacy outcomes were recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS), which were estimated by Kaplan-Meier analysis, with hazard ratios calculated using a multivariate Cox proportional-hazard model. RESULTS AND LIMITATIONS: In this retrospective study of 263 patients with high-grade NMIBC, at a median follow-up of 63 mo, 32% showed recurrence and 15% progressed to muscle-invasive bladder cancer. FGFRa were found in 43% of patients, including 39% mutations and 5.7% fusions. FGFRa were associated with lower rates of concomitant carcinoma in situ. Among patients with or without FGFRa, there was no significant difference in PFS, RFS, and DSS in those who were BCG treated or BCG naive, or in the overall population. Limitations include the retrospective design from a single-center setting. CONCLUSIONS: In patients with high-risk NMIBC, FGFRa were frequently observed. Patients with FGFRa who often exhibit recurrence/relapse after BCG treatment have a high unmet need. PATIENT SUMMARY: Our retrospective study suggests that fibroblast growth factor receptor alterations (FGFRa) occur frequently in non-muscle-invasive bladder cancer (NMIBC). Outcomes were similar with or without FGFRa in patients with NMIBC, both overall and for standard bacillus Calmette-Guérin (BCG) treatment.	bladder
SEOM-SOGUG clinical guideline for localized muscle invasive and advanced bladder cancer (2021).	Most muscle-invasive bladder cancer (BC) are urothelial carcinomas (UC) of transitional origin, although histological variants of UC have been recognized. Smoking is the most important risk factor in developed countries, and the basis for prevention. UC harbors high number of genomic aberrations that make possible targeted therapies. Based on molecular features, a consensus classification identified six different MIBC subtypes. Hematuria and irritative bladder symptoms, CT scan, cystoscopy and transurethral resection are the basis for diagnosis. Radical cystectomy with pelvic lymphadenectomy is the standard approach for muscle-invasive BC, although bladder preservation is an option for selected patients who wish to avoid or cannot tolerate surgery. Perioperative cisplatin-based neoadjuvant chemotherapy is recommended for cT2-4aN0M0 tumors, or as adjuvant in patients with pT3/4 and or pN + after radical cystectomy. Follow-up is particularly important after the availability of new salvage therapies. It should be individualized and adapted to the risk of recurrence. Cisplatin-gemcitabine is considered the standard first line for metastatic tumors. Carboplatin should replace cisplatin in cisplatin-ineligible patients. According to the EMA label, pembrolizumab or atezolizumab could be an option in cisplatin-ineligible patients with high PD-L1 expression. For patients whose disease respond or did not progress after first-line platinum chemotherapy, maintenance with avelumab prolongs survival with respect to the best supportive care. Pembrolizumab also increases survival versus vinflunine or taxanes in patients with progression after chemotherapy who have not received avelumab, as well as enfortumab vedotin in those progressing to first-line chemotherapy followed by an antiPDL1/PD1. Erdafitinib may be considered in this setting in patients with FGFR alterations. An early onset of supportive and palliative care is always strongly recommended.	bladder
Magnetic resonance imaging of bladder pheochromocytomas: a review.	Bladder pheochromocytomas (PCCs) are rare tumors that account for 0.06% of all bladder tumors and makeup 1% of all PCCs. Most PCCs are functional, and they secrete catecholamines that lead to clinical symptoms such as paroxysmal hypertension, headaches, palpitations, and sweating. However, some are nonfunctional and asymptomatic and are hence difficult to diagnose. Cystoscopy and biopsy should not be performed when bladder PCCs are suspected. They may provoke a hypertensive crisis if preventative antiadrenergic blockers are not administered prior to the procedure. The diagnostic workup begins with obtaining blood or urine catecholamine and catecholamine metabolite values to make a presumptive diagnosis of bladder PCC. Computed tomography (C.T.) and magnetic resonance imaging (MRI) are then used to localize and stage the tumor for surgical resection. MRI, due to its superior soft tissue resolution and the ability to use multiparametric MRI (mpMRI) to differentiate between layers of the bladder wall and from other bladder masses, is the optimal imaging modality to detect extra-adrenal bladder PCCs and determine locoregional staging. Once antiadrenergic medications are given, the tumor is resected, and the diagnosis is confirmed histologically. However, the differential diagnosis of bladder PCC often gets overlooked, leading to surgical resection in the absence of antiadrenergic medications, increasing the chances of a fatal hypertensive crisis. This makes MRI an essential diagnostic tool for staging bladder PCCs before surgery. This review discusses the indications for MRI in bladder PCCs and describes findings from these tumors on various MRI sequences and when to use them. We also discuss how MRI can differentiate bladder PCCs from other bladder neoplasms.	bladder
Effectiveness of pembrolizumab in patients with urothelial carcinoma receiving proton pump inhibitors.	BACKGROUND: The association of concurrent proton pump inhibitor (PPI) use with treatment outcome of metastatic urothelial carcinoma (UC) remains controversial. MATERIALS AND METHODS: We retrospectively analyzed the records of 227 patients with platinum-treated metastatic UC treated with pembrolizumab. The primary outcome was overall survival (OS). Immune progression-free survival (iPFS) and objective response per immune response evaluation criteria in solid tumors were also compared. Inverse probability of treatment weighting (IPTW)-adjusted multivariable Cox regression models and an IPTW-adjusted multivariable logistic regression model were used to evaluate the oncological outcomes. Furthermore, the heterogeneity of the treatment effect on OS was examined using interaction terms within the IPTW-adjusted univariate Cox regression models. RESULTS: Overall, 86 patients (37.9%) used PPIs. After weighting, no significant differences in patient characteristics were observed between PPI users and non-users. PPI use was significantly associated with a shorter OS (hazard ratio [HR]: 2.02, 95% confidence interval [CI]: 1.28-3.18, P = 0.003) and iPFS (HR: 1.70, 95% CI: 1.23-2.35, P = 0.001). Although not statistically significant, PPI use was associated with objective response as well (OR: 0.61, 95% CI: 0.36-1.02, P = 0.06). The interaction analyses showed that the effect of PPI significantly decreased with age (HR: 0.97, 95% CI: 0.93-1.00, P[interaction] = 0.048) and was increased in males (HR: 2.97, 95% CI: 1.10-8.05, P[interaction] = 0.032). CONCLUSIONS: PPI use was significantly associated with worse survival of patients with metastatic UC treated with pembrolizumab. Furthermore, the results suggested that its effects decreased with age and was increased in males.	bladder
PRMT5-activated c-Myc promote bladder cancer proliferation and invasion through up-regulating NF-κB pathway.	AIM: PRMT5 and c-Myc were considered as oncogene of bladder cancer. Nevertheless, whether the interaction between of PRMT5 and c-Myc affect bladder cancer progress is unknown. Herein, we explore the above points and discuss deeply its' potential mechanism. METHOD: 5637 and T24 cells were study subjects in vitro. Western blot was used to examined the protein expression. CCK8 and transwell assay were used to analyze proliferation and invasion ability. Additionally, xenograft tumor model was established. Mice imaging experiment, Immunochemistry assay and western blot were carried out. RESULT: Western blot result showed successful transfection of PRMT5-siRNA and c-Myc-siRNA. PRMT5-siRNA could inhibit c-Myc expression, and decrease the proliferation and invasion of bladder cells. And c-Myc overexpression could reverse inhibitory action caused by PRMT5 silence. And in vitro studies found low-expression of c-Myc reduced proliferation and invasion of tumor cells and make the NF-κB pathway inactivation. In vivo studies also demonstrated that inhibiting PRMT5 could downregulate c-Myc expression and inhibit the bladder cancer progress, and the potential mechanism was likely to be related to NF-κB signaling pathway. CONCLUSION: In a word, low-expression of PRMT5 suppressed c-Myc, and thus inhibited proliferation and invasion ability of 5637 and T24 cells through NF-κB pathway.	bladder
Disparities in patient and system factors explain racial/ethnic disparities in delayed time to treatment in muscle invasive bladder cancer.	PURPOSE: Treatment delays in muscle invasive bladder cancer (MIBC) have been shown to be associated with worse outcomes. While every attempt is made to provide adequate treatment expeditiously, Black and Hispanic patients often experience delays at a higher rate than their White counterparts. This study aims to quantify the mechanisms that contribute to this disparity in treatment delay. METHODS: Retrospective analysis of clinical T-stages II-IVa MIBC patients who underwent surgical resection from 2004 to 2017 in the National Cancer Database. A causal inference mediation analysis using the counterfactual framework was implemented to estimate the extent to which racial/ethnic disparities in patient and system factors explain the racial/ethnic disparities in time to treatment. Mediators included income, education, comorbidities, insurance, and hospital type. RESULTS: Among 22,864 patients who met inclusion criteria, 7%, 3%, 2% were of Black, Hispanic, and Other race/ethnicity, respectively. In multivariable models, compared to White patients, Black, and Hispanic patients were associated with 26% (odds ratio = 1.26, 95% confidence interval = 1.12-1.42) and 29% (odds ratio = 1.29, 95% confidence interval = 1.07-1.55) increased odds of having a treatment delay relative to White patients. Mediation analyses suggested that 49% and 26% the treatment delay among Black and Hispanic patients, respectively, could be removed if an intervention equalized the distribution of academic treatment, education, and insurance status to that of White patients. Treatment at an academic hospital and education were the mediators that explained the largest portion of the racial/ethnic disparity in treatment delay. CONCLUSION: Black and Hispanic MIBC patients experience treatment delays when compared to White patients. Intervening upon patient and system factors could reduce substantial treatment delays. Future research is needed to identify other causes of disparities in treatment delays and may help population health initiatives to address racial/ethnic disparities in clinical settings.	bladder
Biomarkers in muscle invasive bladder cancer.	Muscle invasive bladder cancer (MIBC) carries a poor prognosis with a 5-year overall survival rate of 40-50%. For localized disease, radical treatment options are cystectomy or radiotherapy with or without a radiosensitiser. Neoadjuvant or adjuvant chemotherapy is often delivered in addition to either. Metastatic disease can be treated with palliative systemic chemotherapy or immunotherapy. Standard clinicopathological information is insufficient to guide treatment decisions in several clinical scenarios in MIBC and there has been substantial effort to identify predictive and prognostic biomarkers. Despite this, no biomarker has been sufficiently qualified in prospective clinical trials to justify routine use. In this chapter we discuss these biomarkers and provide insight into the significant unmet need for robust biomarkers to inform treatment decisions and ultimately improve outcomes for bladder cancer patients.	bladder
Osteosarcoma of the bladder: a case report.	BACKGROUND: Osteosarcoma arising from the bladder is extremely rare, with only 38 cases reported to our knowledge. It is often detected owing to hematuria, and is treated by surgery (for example, total cystectomy), radiation therapy, and chemotherapy; however, the prognosis is extremely poor. CASE PRESENTATION: An 83-year-old Japanese man underwent cystoscopy for postoperative follow-up of urothelial carcinoma of the bladder, which revealed a 2-cm nodular tumor on the right wall. He had a history of abdominal aortic aneurysm and hypertension, and had been smoking 15 cigarettes per day for 45 years. Seven years previously, the patient underwent transurethral resection of bladder tumor for a 5-cm tumor on the right wall of the bladder. The histopathological diagnosis was urothelial carcinoma. No recurrence had been detected since then. Transurethral resection of bladder tumor was performed, and the histopathological diagnosis was cystosarcoma. Because of his advanced age, we decided that it would be difficult to perform total cystectomy. We therefore performed a second transurethral resection of bladder tumor and found no residual tumor. At 29 months after surgery, the patient remains alive without recurrence. CONCLUSION: Bladder osteosarcoma has a poor prognosis. However, our case was detected early, and treatment with transurethral resection of bladder tumor alone resulted in long-term survival without recurrence.	bladder
Bladder Cancer Extracellular Vesicles Elicit a CD8 T Cell-Mediated Antitumor Immunity.	Tumor-derived extracellular vesicles (TEVs) play crucial roles in mediating immune responses, as they carry and present functional MHC-peptide complexes that enable them to modulate antigen-specific CD8(+) T-cell responses. However, the therapeutic potential and immunogenicity of TEV-based therapies against bladder cancer (BC) have not yet been tested. Here, we demonstrated that priming with immunogenic Extracellular Vesicles (EVs) derived from murine MB49 BC cells was sufficient to prevent MB49 tumor growth in mice. Importantly, antibody-mediated CD8(+) T-cell depletion diminished the protective effect of MB49 EVs, suggesting that MB49 EVs elicit cytotoxic CD8(+) T-cell-mediated protection against MB49 tumor growth. Such antitumor activity may be augmented by TEV-enhanced immune cell infiltration into the tumors. Interestingly, MB49 EV priming was unable to completely prevent, but significantly delayed, unrelated syngeneic murine colon MC-38 tumor growth. Cytokine array analyses revealed that MB49 EVs were enriched with pro-inflammatory factors that might contribute to increasing tumor-infiltrating immune cells in EV-primed MC-38 tumors. These results support the potential application of TEVs in personalized medicine, and open new avenues for the development of adjuvant therapies based on patient-derived EVs aimed at preventing disease progression.	bladder
Feasibility of [(68)Ga]Ga-FAPI-46 PET/CT for detection of nodal and hematogenous spread in high-grade urothelial carcinoma.	BACKGROUND: [(68)Ga]Ga-FAPI-46 is a novel positron emission tomography (PET) ligand that targets fibroblast activation protein (FAP) expression as FAP inhibitor (FAPI) and could already show promising results in several tumor entities. It could be demonstrated that an increased FAP expression correlates with tumor aggressivity in urothelial carcinoma (UC). Given the limited value of [(18)F]FDG in UC, [(68)Ga]Ga-FAPI-46 could add diagnostic information in staging and response assessment in UC. We present the first data of [(68)Ga]Ga-FAPI-46 PET imaging in a pilot cohort of UC patients evaluating uptake characteristics in metastases and primary tumors. METHODS: Fifteen patients with UC prior to or after local treatment underwent [(68)Ga]Ga-FAPI-46 PET/CT imaging for detection of metastatic spread. We compared the biodistribution in non-affected organs and tumor uptake of UC lesions by standard uptake value measurements (SUV(mean) and SUV(max)). Additionally, metastatic sites on PET were compared to its morphological correlate on contrast-enhanced computed tomography (CT). RESULTS: Overall, 64 tumor sites were detected on PET and/or CT. The highest uptake intensity was noted at the primary site (SUV(max) 20.8 (range, 8.1-27.8)) followed by lymph node metastases (SUV(max) 10.6 (range, 4.7-29.1)). In 4/15 (26.7%) patients there were [(68)Ga]Ga-FAPI-46-positive lesions that were missed on standard routine CT imaging. On the other hand, 2/15 patients had suspicious prominent bipulmonary nodules as well as pelvic lymph nodes previously rated as suspicious for metastatic spread on CT, but without increased FAPI expression; here histopathology excluded malignancy. CONCLUSION: [(68)Ga]Ga-FAPI-46 PET shows distinctly elevated uptake in UC lesions. Therefore, the tracer has potential as a promising new biomarker in metastatic UC patients, as [(68)Ga]Ga-FAPI-46 PET might improve detection of metastatic sites compared to CT alone. These findings highly emphasize larger studies investigating FAPI imaging in UC patients.	bladder
Diagnostic performance of nuclear matrix protein 22 and urine cytology for bladder cancer: A meta-analysis.	PURPOSE: To compare and analyze the diagnostic efficacy of nuclear matrix protein 22 (NMP22) and urine cytology (UC) in the diagnosis of bladder cancer. METHODS: Search the Chinese and English studies on NMP22 and urinary cytology in the diagnosis of bladder tumors published between 1999 and June, and conduct quality evaluation, data extraction and analysis. RESULTS: A total of 397 related articles were retrieved, and 12 articles were finally included after screening, including 2456 subjects. The heterogeneity test shows that there is no discernible threshold effect. Perform meta-analysis according to the random effects model. The results showed that the total sensitivity of NMP22 and UC were 0.79 (95% CI [0.73, 0.84]) (CI: Confidence interval), 0.55 (95% CI [0.41, 0.69]), and the total specificity 0.59 (95% CI [0.46], respectively, 0.71), 0.91 (95% CI (0.81, 0.96]), +LR 1.9 (95% CI [1.4, 2.6]) (+LR: positive likelihood ration), 5.9 (95% CI [3.3, 10.6]), -LR 0.35 (-LR: negative likelihood ration), respectively (95% CI [0.27, 0.47]), 0.49 (95% CI [0.38, 0.64]), diagnostic odds ratios 5 (95% CI [3, 9]), 12 (95% CI [7, 21]). The area under the summary receiver operating characteristics curve (AUC) was 0.79 (95% CI [0.75, 0.82]) and 0.81 (95% CI [0.77, 0.84]), respectively. CONCLUSIONS: NMP22 has moderate diagnostic efficiency for bladder cancer. Its sensitivity is greater than UC, but its specificity is significantly lower than that of UC. At present, it cannot replace traditional cystoscopy and UC, but it can be combined to detect bladder tumors. It plays a major role in screening, postoperative monitoring and follow-up.	bladder
Severe diffuse proliferative bronchiolitis complicating culture-proven disseminated BCG infection after intravesical instillation for bladder cancer.	A man in his 70s was admitted to hospital following several months of dyspnoea, night sweats, weight loss and, latterly, fevers. His symptoms correlated with a second maintenance cycle of intravesical BCG instillation for superficial bladder cancer. Blood tests showed raised C-reactive protein, alkaline phosphatase and gamma-GT, although extensive further investigations did not reveal any specific cause. Treatment for a presumed diagnosis of disseminated BCG infection was started, following which his fevers ceased. Later available results of liver biopsy taken prior to treatment supported this diagnosis, and mycobacterial blood and urine cultures grew Mycobacterium bovis Recovery was complicated by a severe diffuse proliferative bronchiolitis which responded to corticosteroids. This case highlights an important dichotomy in the pathophysiology of disseminated BCG infection. It demonstrates how morbidity can be caused by both a direct dissemination of the organism and an immune hypersensitivity response in the same patient.	bladder
Reclassifying pT3 renal pelvic urothelial carcinoma with renal parenchyma invasion to pT2 improves correlation with overall survival.	The American Joint Cancer Committee pT categorization in renal pelvic carcinoma defines pT3 as invasion of renal parenchyma, invasion of peripelvic fat, or both. However, survival heterogeneity within the pT3 category has been demonstrated. This investigation sought to compare survival between pT categories of renal pelvic urothelial carcinoma and identify modifications to improve correlation with survival. Pathology reports from nephroureterectomies performed at our institution from 2010 to 2019 were analyzed to identify primary renal pelvic urothelial carcinoma (n = 146). Tumors were stratified based on pT, pN, and invasion of renal parenchyma vs invasion of peripelvic fat with or without renal parenchyma invasion. Kaplan-Meier survival curves and Cox regression multivariate analysis were used to compare overall survival between groups. Similar survival curves were observed for pT2 and pT3 tumors. Multivariate analysis confirmed overlapping hazard ratios (HRs) for pT2 (HR = 2.64, 95% confidence interval [CI] = 0.69, 10.06) and pT3 (HR = 4.42, 95% CI = 2.08, 9.37). pT3 tumors with peripelvic fat invasion, regardless of renal parenchyma involvement, had a 3.3-fold worse overall survival than pT3 tumors with only renal parenchyma involvement. Additionally, pT3 tumors with only renal parenchyma invasion had similar survival compared to pT2, while pT3 tumors with peripelvic fat invasion had worse overall survival (p = 0.00091). Reclassifying renal parenchyma invasion as pT2 yielded greater survival curve separation and greater difference in HRs. For renal pelvic urothelial carcinoma, modifying the pT3 category to only include tumors with peripelvic fat invasion and expanding the pT2 category to include renal parenchyma invasion may improve pT correlation with overall survival.	bladder